Field of the Invention
The present invention is generally directed to a non invasive treatment for ocular pathology, and relates more particularly to a device and method for generating high intensity focused ultrasound onto at least one annular segment of the ciliary body of an eye affected by glaucoma
Description of Related Art
In the field of ophthalmologic disease, it is well known that glaucoma is a significant public health problem, between 1 to 2% of population being suffering from this pathology, because glaucoma is a major cause of blindness.
The World health organisation considers glaucoma as the second cause of blindness in the world, responsible of 15% of declared blindness occurrences, with an incidence of 2.4 millions persons per year.
The evolution of glaucoma is slow. Glaucoma is an insidious health disease because at the first stage glaucoma is asymptomatic; the patient does not feel any pain or any visual problem. When the first visual troubles appear, lesions are commonly already large and despite irreversible.
The blindness that results from glaucoma involves both central and peripheral vision and has a major impact on an individual's ability to lead an independent life.
Glaucoma is an optic neuropathy, i.e. a disorder of the optic nerve, which usually occurs in the setting of an elevated intraocular pressure. The pressure within the eye increases and this is associated with changes in the appearance and function of the optic nerve. If the pressure remains high for a long period of time (many years), total vision loss occurs. High pressure develops in an eye because of an internal fluid imbalance.
The eye is a hollow structure composed of two segments: the anterior segment between the cornea and the crystalline lens, and the posterior segment between the crystalline lens and the retina. The anterior segment contains a clear fluid called “aqueous humor.” Aqueous humor is formed in the posterior chamber of the anterior segment of the eye by the ciliary body. The fluid, which is made at a fairly constant rate, then passes around the lens, through the pupillary opening in the iris and into the anterior chamber of the eye. The fluid drains out of the eye mainly through the trabecular meshwork and Schlemm's canal.
With the increased pressure in the eye, the aqueous fluid builds up because it cannot exit fast enough. As the fluid builds up, the intraocular pressure (IOP) within the eye increases. The increased IOP compresses the axons in the optic nerve and also may compromise the vascular supply to the optic nerve. The optic nerve carries vision from the eye to the brain. Some optic nerves seem more susceptible to abnormally elevated IOP than other eyes.
The only therapeutic approach currently available in glaucoma is to reduce the intraocular pressure. The objective is not to restore lost vision, because lesions are not reversible, but to preserve residual vision.
The clinical treatment of glaucoma is approached in a step-wise fashion. Medication often is the first treatment option except for congenital glaucoma wherein surgery is the primary therapy.
Administered either topically or orally, these medications work to either reduce aqueous production or they act to increase outflow. Currently available medications may have many serious side effects including: congestive heart failure, respiratory distress, hypertension, depression, renal stones, aplastic anemia, sexual dysfunction and death.
The commonly used medications are Prostaglandin or analogs like latanoprost (Xalatan), bimatoprost (Lumigan) and travoprost (Travatan) which increase uveoscleral outflow of aqueous humor; Topical beta-adrenergic receptor antagonists such as timolol, levobunolol (Betagan), and betaxolol which decrease aqueous humor production by the ciliary body; Alpha2-adrenergic agonists such as brimonidine (Alphagan) which work by a dual mechanism, decreasing aqueous production and increasing uveo-scleral outflow; Less-selective sympathomimetics like epinephrine and dipivefrin (Propine) which increase outflow of aqueous humor through trabecular meshwork and possibly through uveoscleral outflow pathway; Miotic agents (parasympathomimetics) like pilocarpine which work by contraction of the ciliary muscle, tightening the trabecular meshwork and allowing increased outflow of the aqueous humour; Carbonic anhydrase inhibitors like dorzolamide (Trusopt), brinzolamide (Azopt), acetazolamide (Diamox) which provide a reduction of aqueous humor production by inhibiting carbonic anhydrase in the ciliary body. The two most prescribed medications are currently topical Prostaglandin Analogs and Betablockers.
Compliance with medication is a major problem, with estimates that over half of glaucoma patients do not follow their correct dosing schedules. Fixed combinations are also prescribed extensively since they improve compliance by simplifying the medical treatment.
When medication fails to adequately reduce the pressure, often surgical treatment is performed as a next step in glaucoma treatment. Both laser and conventional surgeries are performed to treat glaucoma. In many cases, these operations are a temporary solution, as there is not yet a cure which is completely satisfactory for glaucoma.
There are two different approaches to treat glaucoma: either the surgeon tries to improve aqueous humor drainage, or he tries to reduce its production.
The most practiced surgeries intended to improve the aqueous humor drainage are: canaloplasty, laser trabeculoplasty, laser peripheral iridotomy (in case of angle closure glaucoma), trabeculectomy, deep non perforating sclerectomy and glaucoma drainage implants.
The most practiced surgery intended to reduce aqueous humor production is the cyclodestruction technique. When cyclodestruction is performed with a laser, it is called cyclophotocoagulation. High Intensity focused Ultrasound can be used to obtain a cyclodestruction.
Canaloplasty is an advanced, non penetrating procedure designed to enhance and restore the eye's natural drainage system to provide sustained reduction of IOP. Canaloplasty utilizes breakthrough micro catheter technology in a simple and minimally invasive procedure. To perform a canaloplasty, a doctor will create a tiny incision to gain access to a canal in the eye. A micro catheter will circumnavigate the canal around the iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material. The catheter is then removed and a suture is placed within the canal and tightened. By opening the canal, the pressure inside the eye will be relieved.
Laser trabeculoplasty may be used to treat open angle glaucoma. A laser spot is aimed at the trabecular meshwork to stimulate opening of the mesh to allow more outflow of aqueous fluid. Usually, half of the angle is treated at a time.
There are two types of laser trabeculoplasty:                Argon laser trabeculoplasty (ALT) uses a laser to open up the drainage angle of the eye.        Selective laser trabeculoplasty (SLT) uses a lower-level laser to obtain the same result.        
Laser peripheral iridotomy may be used in patients susceptible to or affected by angle closure glaucoma. During laser iridotomy, laser energy is used to make a small full-thickness opening in the iris. This opening equalizes the pressure between the front and back of the iris, causing the iris to move backward.
The most common conventional surgery performed for glaucoma is the trabeculectomy. Here, a partial thickness flap is made in the scleral wall of the eye, and a window opening made under the flap to remove a portion of the trabecular meshwork. The scleral flap is then sutured loosely back in place. This allows fluid to flow out of the eye through this opening, resulting in lowered intraocular pressure and the formation of a bleb or fluid bubble on the surface of the eye.
Trabeculectomy is associated with many problems. Fibroblasts that are present in the episclera proliferate and migrate and can scar down the scleral flap. Failure from scarring may occur, particularly in children and young adults. Of eyes that have an initially successful trabeculectomy, eighty percent will fail from scarring within three to five years after surgery. To minimize fibrosis, surgeons now are applying antifibrotic agents such as mitomycin C (MMC) and 5-fluorouracil (5-FU) to the scleral flap at the time of surgery. The use of these agents has increased the success rate of trabeculectomy but also has increased the prevalence of hypotony. Hypotony is a problem that develops when aqueous flows out of the eye too fast. The eye pressure drops too low (usually less than 6.0 mmHg); the structure of the eye collapses and vision decreases. Antimetabolites directly applied on the surgical site can be used in order to improve the surgical prognosis, especially in high risk of failure (black patients, juvenile glaucoma . . . ).
Trabeculectomy creates a pathway for aqueous fluid to escape to the surface of the eye. At the same time, it creates a pathway for bacteria that normally live on the surface of the eye and eyelids to get into the eye. If this happens, an internal eye infection can occur called endophthalmitis. Endophthalmitis often leads to permanent and profound visual loss. Endophthalmitis can occur anytime after trabeculectomy. Another factor that contributes to infection is the placement of a bleb. Eyes that have trabeculectomy performed inferiorly have about five times the risk of eye infection than eyes that have a superior bleb. Therefore, initial trabeculectomy is performed superiorly under the eyelid, in either the nasal or temporal quadrant.
In addition to scarring, hypotony and infection, there are other complications of trabeculectomy. The bleb can tear and lead to profound hypotony. The bleb can be irritating and can disrupt the normal tear film, leading to blurred vision. Patients with blebs generally cannot wear contact lenses. All of the complications from trabeculectomy stem from the fact that fluid is being diverted from inside the eye to the external surface of the eye.
More recently a new surgical technique has been described, called Non-perforating deep sclerectomy ab externo. This technique allows avoiding to open the anterior chamber of the eye and consequently reduces the risk of postoperative complications. The major limitation of this technique is that it is a very difficult surgical technique and only a few surgeons are able to perform it successfully.
When trabeculectomy or sclerectomy doesn't successfully lower the eye pressure, the next surgical step often is an aqueous shunt device. There are several different glaucoma drainage implants. These include the original Molteno implant, the Baerveldt tube shunt, or the valved implants, such as the Ahmed glaucoma valve implant or the ExPress Mini Shunt and the later generation pressure ridge Molteno implants. These are indicated for glaucoma patients not responding to maximal medical therapy, with previous failed guarded filtering surgery (trabeculectomy). The flow tube is inserted into the anterior chamber of the eye and the plate is implanted underneath the conjunctiva to allow flow of aqueous fluid out of the eye into a chamber called a bleb.
The prior art includes a number of such aqueous shunt devices, such as U.S. Pat. No. 4,936,825, U.S. Pat. No. 5,127,901, U.S. Pat. No. 5,180,362, U.S. Pat. No. 5,433,701, U.S. Pat. No. 4,634,418, U.S. Pat. No. 4,787,885, U.S. Pat. No. 4,946,436, U.S. 20040015140A1 and U.S. Pat. No. 5,360,399.
Many complications are associated with aqueous shunt devices. A thickened wall of scar tissue that develops around the plastic plate offers some resistance to outflow and in many eyes limits the reduction in eye pressure. In some eyes, hypotony develops because the flow through the tube is not restricted. The surgery involves operating in the posterior orbit and many patients develop an eye muscle imbalance and double vision post-operatively. Moreover, because they are open to the surface of the eye, a pathway is created for bacteria to get into the eye and endophthalmitis can potentially occur.
All the strategies mentioned above are intended to improve aqueous humor drainage. Another strategy consists in destroying a significant proportion of a circular intraocular organ, placed behind the iris: the ciliary body. This organ and particularly the double layer epithelium cells are responsible for aqueous humor production. The destruction of a significant proportion of the ciliary body, technique called cyclodestruction, reduces the production of aqueous humor and consequently reduces the Intra Ocular Pressure.
The most common technique currently used is the cyclophotocoagulation obtained with a laser diode (810 nm). During cyclophotocoagulation surgery, the surgeons point a laser at the white part of the eye (sclera). The laser passes through the sclera to the ciliary body. The laser damages parts of the ciliary body so that it will produce less aqueous humor, which lowers eye pressure. The procedure is performed with local anaesthesia. The problem with cyclophotocoagulation is that one shot destroys only a small region of ciliary body and many shots are necessary all around the eye globe, so that a sufficient part of the ciliary body is destroyed. At each point the surgeon places manually the laser applicator in contact with the sclera approximately at 2 mm from the limbus and with an incidence ideally perpendicular to the surface of the eye. Then he performs a laser shot. Then he moves the applicator to the next site for a new laser shot. This manual technique is quite empiric, non reproducible, long and not easy. Moreover, the surgeon starts the laser shot without any control on the precise position and direction of the laser beam and without any feedback on the result of the shot on the ciliary body.
DE 44 30 720 describes an apparatus for diode laser cyclophotocoagulation to improve the technique and reduce the risk of empiric manipulation. As shown on FIGS. 2a and 3 of DE 44 30 720, the apparatus comprises laser means (3, 33) for applying laser radiation for cyclophotocoagulation, an ultrasonic head (4, 40) of an ultrasonic bio microscope for monitoring said laser cyclophotocoagulation, and fixing means for holding the laser means and the ultrasonic head.
The ultrasonic head generates low intensity ultrasounds to obtain high resolution echographic images of the region to be treated.
The fixing means serves both to stabilize the patient's eye in the course of the treatment and also to keep the liquid in place on the patient's eye. The fixing means comprise two cylinders: an outer cylinder 20a, and an inner cylinder 20b. The outer cylinder is adapted to be disposed on the eye of the patient. The inner cylinder is destined to support the laser means and the ultrasonic means. The inner cylinder is adjoined to the outer cylinder and is adapted to rotate relative to the outer cylinder.
As described in DE 44 30 720, during the treatment, the laser means generate laser radiations punctually for cyclophotocoagulation of a punctual zone of the region to be treated. Then, the ultrasonic head and the laser means are displaced by rotating the inner cylinder in order to treat another punctual zone of the region of interest. These steps are repeated until all the circumference of the eye has been treated.
This method presents the inconvenient that it is necessary to repeat the operation (i.e. rotate the inner cylinder, acquire an image, verify that the apparatus is still in place, produce a laser shot) many times to treat the whole region to be treated. In other words, the operation have to be repeated many times so that the all the circumference of the eye can be treated.
Furthermore, this method may induce damages to the visual functions (due to spot size errors, misalignment between the ultrasonic head, the laser means and the fixing means, etc.).
Moreover, considering the region which is treated (i.e. the eye) and the size of such apparatus, it is easy to imagine the difficulties of manipulating such apparatus, and in particular to rotate the inner cylinder comprising the laser means and the ultrasonic means without inducing displacements of the outer cylinder.
Finally, the need of repeating an operation many times increases the operative time and thus the error risk factor.
To overcome these drawbacks, it has been already imagined using controlled ultrasonic energy in the treatment of glaucoma. “Therapeutic ultrasound in the treatment of glaucoma. I. Experimental model—Coleman D J, Lizzi F L, Driller J, Rosado A L, Chang S, Iwamoto T, Rosenthal D—PMID: 3991121 (PubMed) 1985 March; 92(3): 339-46” discloses a treatment of glaucoma applying High Intensity Focused Ultrasound (HIFU) onto the ciliary body to provide filtration and focal disruption of ciliary epithelium treating elevated intraocular pressure in a non invasive manner. An apparatus associated to this treatment using controlled ultrasonic energy in the treatment of glaucoma is also described in U.S. Pat. No. 4,484,569. However, such apparatus which was manufactured and distributed under the commercial name of SONOCARE was very difficult to manipulate. Moreover such apparatus allows to treat only one punctual zone at a time. Thus—as disclosed above with regard to laser techniques—each shot needs to be repeated many time to treat all the circumference of the eye and all the apparatus needs to be handled, placed and calibrated many times, thus taking a very long time (i.e. displacement of the ultrasonic means, verification of the position of the ultrasonic means with regard to the punctual region to be treated with optical and echographic sighting means, filling of the device with coupling liquid and production of a ultrasonic shot).
In the same manner, the prior art includes the international patent application WO 02/38078 teaching a method of treating an eye, including glaucoma, that comprises the steps of identifying an area of an eye, such as Schlemm's canal for example, focusing a device capable of directing HIFU energy on the area, such as transducer of 4 to 33 mm range, generating HIFU energy from the device onto the area wherein the energy transfer from the device to the area results in an increase in temperature of the area.
Even if this method provides a treatment to glaucoma in a non invasive manner, it presents the inconvenient that it is necessary to repeat the operation many times to treat the eye circumferentially.
Moreover, tissues at the neighbourhood of the treatment area can be destroyed leading to blurred vision, eye muscle imbalance or double vision. It is therefore necessary to use an imaging system like a scan ultrasonography or a Magnetic Resonance Imaging system said MRI to identify the area to be treated with the greatest precision and to measure changes in the subject eye after each operation.
It is consequently hard and expensive to apply this method in the treatment of glaucoma.